David Remnick: It's rare that a drug has had as big an impact on our lives as Ozempic. It's been on the market for a relatively short time, and something like 12% of Americans have taken Ozempic or one of the others in its class, the GLP-1 drugs. Now, 12% is a lot, but when you consider that around 40% of us are obese, we're probably not at the plateau for GLP-1 drugs. Because these are relatively new drugs, there's a lot that scientists don't know about them yet. Dhruv Khullar is a contributing writer covering medicine and healthcare, and he just published a piece of reporting in the New Yorker called Can Ozempic Cure Addiction?

Dhruv Khullar: This segment will be called Everyone's Doing It. Doing It, Doing It.

David Remnick: [chuckles] God. Are you willing to admit it's a wonder drug?

Dhruv Khullar: I don't know about a wonder drug, but it's the closest thing we have.

David Remnick: How did you get clued into this research on GLP-1 drugs, Ozempic, Wegovy, and so many others, and then tie it to the problem of addiction?

Dhruv Khullar: I've been interested in these drugs forever, in part because we saw they can manage diabetes and then obesity, but not just that. It's not just an aesthetic thing with these drugs. If you think about cardiovascular risk, stroke risk, chronic kidney disease, liver disease, all these things seem to be getting better the longer that people are on these drugs. Then there's just all these stories, these anecdotes from people who start taking the drugs. They don't feel like drinking anymore, they don't feel like smoking, they're not doing opioids, they don't want to gamble, they don't want to shop.

There's an avalanche of these stories. Then you start to get these clinical trials, and that's what we're trying to unpack. Is this something that's actually true and happening, or is it just on Instagram?

David Remnick: How long have these drugs been around? Because to the average person, they started hearing about them a couple years ago, through Hollywood and gossip magazines, and who's lost 50 pounds, and so on. They've been in your life as a physician for how long?

Dhruv Khullar: More than 20 years. People don't realize this, but the first GLP-1 on market came about in 2005, and you had to take it twice a day. Then there were the next generation, about five--

David Remnick: People were taking it mainly for diabetes.

Dhruv Khullar: Only for diabetes, basically. The next generation is about five, seven years later, you get drugs that you can take once a day. Then the real big shift happens when scientists tinker with these molecules, and they last in your body for a week or more. That's when you start seeing these huge amounts of weight loss, that people are just losing weight as they start to take these medications. That happen around 2017, 2018, and then a few years later, it blows up on social media. That's where it becomes a global phenomenon. Everyone is talking about these drugs, everyone wants to be on these drugs.

David Remnick: When did it become apparent that it had this really marked effect on addiction?

Dhruv Khullar: It's still becoming apparent. It's not 100% clear cut that that's the case, but basically, drugs are approved based on studies of several hundred carefully selected individuals. There's only so much information you can get when you study a few hundred people who are all healthy and don't have comorbidities. That's how you get a drug approved. Now we're in the midst of this massive social experiment where tens of millions of people are taking these medications. All sorts of things are happening, and people are responding to them in all sorts of ways.

Amidst that explosion of use, we're seeing more and more people reporting, "Hey, I don't feel like drinking, I don't feel like smoking." It seems to be doing something more fundamental than slowing down food in your GI tract or controlling your blood sugar, but really playing with the reward system in your brain.

David Remnick: I hear people I know who take this for weight loss say the following to me, "I hear less food noise in my brain." What does that mean?

Dhruv Khullar: It means that they're ruminating less on food. They're having fewer of these intrusive, repetitive thoughts about wanting to eat food, thinking about food, when's my next meal? All those things people have reported with food. They're increasingly reporting that with alcohol or with cocaine or with any number of other potentially addictive behaviors and substances. What seems to be happening is we've thought about these drugs as drugs that are affecting the body in the way of diabetes and obesity, but they are fundamentally learning psychoactive drugs. They're playing with the reward system in the brain. There are potentially huge benefits of that, but obvious drawbacks as well.

David Remnick: What are the drawbacks?

Dhruv Khullar: Some people who take these drugs report loss of not just desire for food or alcohol, but loss of desire for pretty much everything. You have this phenomenon of what's called anhedonia.

David Remnick: What pleasures are we talking? Are we talking about sex or hunger, or--

Dhruv Khullar: Yes, sex. I spoke to a woman for this piece that loved gardening. That was one of the joys of her life. She bought these beautiful Japanese maple trees to plant, and she just watched them wither in her backyard. She eventually closed the windows because she didn't want to look at her.

David Remnick: Because she was taking Ozempic.

Dhruv Khullar: Because she started taking Ozempic.

David Remnick: Are we sure it's because she was taking Ozempic?

Dhruv Khullar: You can never be sure, but at least in her experience, she stopped taking it, and her mood got better, and she felt excited to live in the way that she was before. There are people on Reddit, patients I've spoken to, who have reported in a minority of cases-- I don't want to oversell this, but it is the case that some people, for somewhat unknown and mysterious reasons, experience the negative impact of these medications. People have started talking about them broadly as moderation molecules. They help you moderate your desire for all sorts of potential vices.

At the same time, for some people, they go too far. They turn into desire dampeners, where everything that you enjoyed doing in the past, you have more and more difficulty enjoying those things.

David Remnick: Explain the science of this. What molecule is it working on? I didn't know that there was a desire molecule that ranged from ice cream to sex to cocaine.

Dhruv Khullar: Yes. Primarily, the traditional telling of the molecule GLP-1, it's a tiny molecule in your body that dissolves within minutes. That's what happens in our body normally. What it does is a few main things. It attaches to receptors in your pancreas. It gets you to secrete insulin. It attaches to receptors in your GI tract, it slows down the stomach, and then there are receptors in the brain. What it does there is helps increase the sense of satiety.

As we're learning more about the molecules and as we've transformed them from lasting for just a few minutes in the body to hours and then days, we're seeing more and more potent effects. Again, bear with me for a second, but we're getting to this place, we're understanding that they're modulating what's called the mesolimbic pathway, which is sometimes called the brain's reward system. When you're doing that, what it seems to be doing is a few things. Some of this is an animal study, some of it is in human studies, but it's lowering the dopamine spikes that we receive from checking social media or from cocaine use or compulsive shopping, you name it.

It seems to be doing that without draining the baseline levels of dopamine. You can imagine just getting rid of dopamine altogether and turning you into a listless person who can't do anything. It doesn't seem to be doing that. What it seems to be doing is just calming the waters, which is why we see people don't receive as much of a hit or desire to use some of these things.

David Remnick: If I take Ozempic, I'm going to stop looking at my phone every 13 seconds, too?

Dhruv Khullar: I don't want to make that claim just yet. It's not out of the realm of possibility that people who take Ozempic because it's operating on the same reward pathway, you do have a dopamine hit in that area when you check your social media feed. I think that's a totally reasonable thing to study. See how people's social media use is affected when they start Ozempic.

David Remnick: Are drug and alcohol rehabilitation centers using Ozempic now in a concerted way?

Dhruv Khullar: There are some cases of rehab centers starting to use it. I would say that the science is not there yet. We're just starting to get randomized control data.

David Remnick: That takes time.

Dhruv Khullar: It takes time, exactly. You start with the animal models and then a few dozen people, and now there are hundreds of people being enrolled in these trials. I would want to wait for the readout of those trials to understand are these actually, in a systematic way, helping people? I have to say, over the course of my reporting, I became more and more bullish on the idea that these are actually going to be really important molecules for the treatment of addiction.

David Remnick: Now, Dhruv, what are your cautionary signals that you want to send about this new research? There's often a concern in medical reporting that drug makers amplify or exaggerate what they consider to be the good news. Are you concerned about that?

Dhruv Khullar: In this case, drug makers have not been focused enough on addiction. In fact, a lot of this research is not being driven by the drug makers, whether it's Eli Lilly or Novo Nordisk. These are independent researchers in many cases that are hearing the stories of patients and trying to set up clinical trials that are independently funded to try to understand is this working for people in a rigorous way. I'm less concerned about the conflicts of interest for this specific indication than I usually am for many other types of medications.

I think a couple things that are important to note. We've talked about the idea that we don't have the right treatment model in place yet. We don't know when we should start these medications, how long people need to be on them. We don't know whether people will develop tolerance to these medications such that their cravings will return. The psychological effects, at least for some people, could be significant enough that they have to come off the medications.

I think most fundamentally, these drugs aren't doing anything to address the underlying root causes of addiction for a lot of people, that is stress and loneliness and trauma and environmental factors that have put them in a position where they are using drugs as a coping strategy. I think GLP-1s can give you a break. They can provide an opportunity to reset some things in your life, but they're not going to be a comprehensive response.

David Remnick: What are the politics around GLP-1s? RFK Jr. we know is putting a lot of emphasis on ultra processed foods, and he's critical of the pharma industry. Kennedy said in the past, "You could give every American three meals a day of organic food and diabetes would disappear overnight." Put the accuracy of that to one side for a moment. He does have a point about diet. Sure. Does he have a point about medicating obesity instead of tackling the causes?

Dhruv Khullar: Look, I'm all in favor of tackling the causes of obesity. Changing the food environment, changing the built environment, getting people moving more, making sure that everyone has access to healthy food. I don't think anyone would disagree with any of that. The challenge is we haven't really been able to do those things for most people over the past half century while obesity rates have been skyrocketing. There's no argument about changing the underlying causes of obesity. As we're doing that, this is a remarkable advance to help people in the immediate term as they're struggling with all sorts of complications with obesity. To deny people access to that, I think is totally wrongheaded.

David Remnick: They're also a disciplining agent. Right? Ice cream is delicious-

Dhruv Khullar: Yes.

David Remnick: -last time I looked. Alcohol can be just swell.

Dhruv Khullar: Yes.

David Remnick: This acts as a disciplining agent in your life. Is there anything wrong with that?

Dhruv Khullar: As long as it doesn't go too far.

David Remnick: What constitutes too far? What do you mean?

Dhruv Khullar: If you lose pleasure in the things that you otherwise took pleasure in, which for many people includes a glass of wine, or seeing your friends, or gardening, or going out and going for a run. If it starts to shave those things out of your life, that, I think, is the most fundamental potential risk. In another way, you're using a chemical agent to change your desires. There are these second-order desires that are affected as well. The first order desire might be, "I want that cookie." The second order desire is, "I want not to have that cookie."

I talked to one woman who had been having marital problems for years. She started on this medication and within months she left her partner. For most people--

David Remnick: Why?

David Remnick: Because she said, "I had been inhibited by this alcohol noise in my mind, it had been taking up so much energy that I wasn't able to do what I wanted to do," which was ultimately start afresh. This gave her the space to do that. In her case, it seemed like it was the right thing. You could envision people making decisions that are less productive when a substance is changing their desires in a certain way.

David Remnick: How have obesity rates in this country been affected by these drugs?

Dhruv Khullar: I'll say for the first time in the last four decades, we're seeing a plateau and even a decline in obesity rates. I don't think that's by dint of willpower. I think that has something to do with what's happening here with GLP-1 medications. I think the hope is that over time, as more and more people have access to medications, but also as there are newer and newer agents, ones that are just pills instead of injections, different medications will hit different receptors, have different side effect profiles.

I've written in the past that these are potentially some of the most powerful medications in the annals of chronic disease. We have not had a medication in the past that has allowed people to lose weight in the way that these medications do.

David Remnick: Is access a matter of class?

Dhruv Khullar: So far, it is certainly powerfully affected by class. I think that will change over time as there's more and more competitors in the market. As public programs like Medicare and Medicaid potentially start to cover these medications.

David Remnick: They're not covered now?

Dhruv Khullar: Not for the indication of obesity. Medicaid is state-by-state. For Medicare, you can't get it just for obesity. You have to have a secondary issue, whether it's diabetes or something else.

David Remnick: What are the downsides of these drugs that you're hearing about, other than the anhedonia that they might produce?

Dhruv Khullar: There are in mouse models, at least, potential risk for certain types of cancer. People with a history of thyroid cancer, people have experienced pancreatitis, which is inflammation of the pancreas, and people continue to experience significant, in some cases, nausea, vomiting, and even anorexia. The other thing that I should mention here is that when people lose weight, they're also losing muscle. That's particularly problematic for older people who struggle with frailty and not having enough muscle mass. It's important as people are losing this weight that they engage in an exercise regimen, strength training, and potentially increasing protein intake.

David Remnick: If you were overweight, you're not, but if you were overweight, would you take these drugs?

Dhruv Khullar: Absolutely.

David Remnick: You would?

Dhruv Khullar: Yes, if I could tolerate them, if I wasn't having significant psychological side effects, or nausea, or vomiting. I think not just for the purposes of losing weight, but for reducing the risk of obesity related complications. I think it's something that anyone in that position should consider.

David Remnick: Now, I've got to go off topic for a second here, Dhruv, but I think our listeners want to know this. You're a practicing doctor in a big hospital in New York City, in addition to, of course, being a brilliant writer for the New Yorker. You just published an essay in the New Yorker called What "The Pitt" Taught Me about Being a Doctor. The Pitt, obviously, being huge show on HBO. What does the show get right about your world?

Dhruv Khullar: I think that over the past decade, I've tried to communicate the challenges that clinicians, doctors, nurses face when trying to deliver care in this system. That is everything from administrative burdens and quality measurement, and the electronic health record, and climate change, and artificial intelligence, you name it. Somehow, this show has incorporated all of that and turned it into really good TV.

It's like they have imbibed all the important conversations in healthcare and now put it into a compelling narrative that people want to watch. It is accurate, it is entertaining, it captures what is so hard and also what is so beautiful about practicing medicine in the 21st century. For me, it drove home this point that there are all these challenges with the system and there always will be, but there's always room for grace.

David Remnick: Thanks so much, Dhruv.

Dhruv Khullar: Thanks for having me.

David Remnick: You can find Dhruv Khullar writing about the new Ozempic research, changes at the CDC, and much, much more at NewYorker.com.

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